RESUMO
BACKGROUND: Breast cancer and its treatment remains a public health problem. There is still a lack of epidemiological data concerning complications and aesthetic results bound to radiotherapy after an immediate breast reconstruction. The objective of this study was to compare outcomes of immediate breast reconstruction regardless to the use of radiotherapy (history of radiotherapy or adjuvant radiation therapy), in order to determine risk factor of complications and bad aesthetic results. METHODS: We conducted a retrospective study between January 2014 and December 2016 at the hospital "Gustave Roussy" in Paris, concerning breast cancer patients who needed immediate breast reconstruction after total mastectomy. The primary endpoint was to assess the failure rate of reconstruction and the aesthetic result, the secondary endpoint assessed the early and late rate of complications. We realized a multivariate analysis in order to identify risks factors that may predict complications. RESULTS: Three hundred and thirty three patients have been included: 157 in the "radiotherapy group" compared to 176 in the "no radiotherapy group". Preoperative characteristics were comparable. Average follow-up was between 1 and 3years without missing. Patients who benefited from radiotherapy had an equal risk failure of reconstruction. The subgroup analysis revealed non-significant differences: 12.7% failure rate reconstruction in the "radiotherapy group" vs. 12.5%. We could notify a better rate of "excellent results" in the "no radiotherapy group": 35% vs. 8.2%. Secondary outcomes were comparable. CONCLUSIONS: Radiotherapy related to immediate breast reconstruction didn't increase the failure rate of reconstruction or aesthetic results, comparatively to non-irradiated patients. It is therefore permissible to suggest an immediate breast reconstruction to any patients which would benefit from a total mastectomy followed by radiotherapy; in order to prevent them from a secondary breast reconstruction, who could be physically and psychologically more impactful.
Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia , Mastectomia , Complicações Pós-Operatórias/epidemiologia , Adulto , Neoplasias da Mama/radioterapia , Estudos Epidemiológicos , Feminino , Humanos , Mastectomia/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Background: The cyclin-dependent kinase 4 (CDK4)/6 inhibitor Palbociclib is a new standard treatment in hormone-receptor positive breast cancer patients. No predictive biomarkers have been identified and no pharmacodynamics has properly been described so far. Patients and methods: Patients with early-breast cancer were randomized 3 : 1 to oral palbociclib 125 mg daily for 14 days until the day before the surgery versus no treatment. Primary objective was antiproliferative response defined as a natural logarithm of Ki67 expression at day 15 below 1. Secondary end points were subgroups analyses and safety. Exploratory analyses included search for predictive biomarkers. Immunostainings (Ki67, RB, pRB, p16, pAKT, pER, pCDK2, CyclinD1), FISH (CCND1) and gene expression (GE) arrays were carried out at baseline and at surgery. In addition, activating PIK3CA and AKT1 mutations were assessed at baseline. Results: 74 patients were allocated to palbociclib and 26 to control. Most patients (93%) were hormone-receptor (HR)-positive, whereas 8% were HER2-positive. Palbociclib led to significantly more antiproliferative responses when compared with control (58% versus 12%, P < 0.001), and to a significantly higher Ki67 decrease (P < 0.001). In the HR-positive/HER2-negative subgroup, this antiproliferative effect was even more marked in the palbociclib arm when compared with control (70% versus 9%, P < 0.001). Palbociclib treatment led also to a significantly higher decrease from baseline in phospho-Rb when compared with control (P < 0.001). Among treated patients, changes in Ki67 correlated with changes in phospho-Rb (Spearman rank r = 0.41, P < 0.0001). GE analyses confirmed a major effect on proliferation and cell cycle genes. Among treated patients, CCNE2 expression was significantly more decreased in antiproliferative responders versus nonresponders (P = 0.006). Conclusion: Short-term preoperative palbociclib decreases Ki67 in early-breast cancer patients. Early decrease of Rb phosphorylation correlates with drug's effect on cell proliferation and could potentially identify patients with primary resistance. Clinical trial registration: NCT02008734.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/terapia , Proliferação de Células/efeitos dos fármacos , Piperazinas/farmacologia , Piridinas/farmacologia , Proteínas de Ligação a Retinoblastoma/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Administração Oral , Adulto , Idoso , Antineoplásicos/uso terapêutico , Biópsia , Mama/patologia , Neoplasias da Mama/patologia , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/metabolismo , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Antígeno Ki-67/análise , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Fosforilação/efeitos dos fármacos , Piperazinas/uso terapêutico , Piridinas/uso terapêutico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Resultado do TratamentoRESUMO
The Indocyanine green (ICG) is a soluble dye that is eliminated by the liver and excreted in bile. When illuminated by an near-infrared light, the ICG emits fluorescence in the near-infrared spectrum, which can be captured by a near-infrared camera-handled device. In case of intravenous injection, ICG may be used as a marker of skin perfusion. In case of interstitial injection, it may be useful for lymphatic network mapping. In oncological and reconstructive breast surgery, ICG is used for sentinel lymph node identification, to predict mastectomy skin flap necrosis, to assess the perfusion of free flaps in autologous reconstruction and for diagnosis and treatment of upper limb secondary lymphedema. Intraoperative indocyanine green fluorescence might also be used to guide the excision of nonpalpable breast cancer.
Assuntos
Neoplasias da Mama , Angiofluoresceinografia , Mamoplastia/métodos , Mastectomia , Biópsia de Linfonodo Sentinela , Retalhos Cirúrgicos/transplante , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Corantes/administração & dosagem , Feminino , Angiofluoresceinografia/métodos , Humanos , Verde de Indocianina/administração & dosagem , Linfedema/diagnóstico por imagem , Mastectomia/métodos , Mastectomia Segmentar/métodos , Biópsia de Linfonodo Sentinela/métodos , Resultado do TratamentoRESUMO
Immediate breast reconstruction showed many advantages in terms of aesthetic and functional results and improvement of quality of life when compared to delayed breast reconstruction. Previous radiotherapy or the use of adjuvant treatments such as radiation therapy, or chemotherapy are no longer a contraindication for immediate breast reconstruction. However, it is important to respect certain rules in order to decrease the risk of complications: the choice of reconstruction technique, the management of the skin envelope according to the breast shape you want to create, the time delay between the first and the second stage of reconstruction depending on a possible adjuvant treatment.
Assuntos
Algoritmos , Tomada de Decisão Clínica , Mamoplastia , Neoplasias da Mama/cirurgia , Feminino , HumanosRESUMO
Immediate breast reconstruction indications extend to infiltrating carcinomas, due to new matrix implant coverage techniques and the development of perforator flaps. These techniques allow adjuvant treatments. However, the decision of immediate reconstruction must be discussed with the oncological multidisciplinary team and the benefits/risks must also be evaluated in relation to the morphology of the patients and their co-morbidities. The chosen type of mastectomy: conventional or skin sparing and/or nipple sparing depends on the shape and volume of the breast, the localization of the tumor in the breast and the distance from the nipple areola complex (NAC). We describe an algorithm to allow, in the case of therapeutic mastectomy with or without adjuvant radiotherapy, an immediate reconstruction with implants or free or pedicled flaps.
Assuntos
Algoritmos , Tomada de Decisão Clínica , Mamoplastia , Mastectomia , Neoplasias da Mama/cirurgia , Feminino , HumanosRESUMO
BACKGROUND: The detection of synchronous metastases at primary diagnosis of breast cancer (BC) affects its initial management. A risk calculator that incorporates many factors to evaluate an individual's risk of harbouring synchronous metastases would be useful to adapt cancer management. PATIENTS AND METHODS: Patients with primary diagnosis of BC were identified from three institutional databases sharing homogeneous work-up recommendations. A risk score for synchronous metastases was estimated and a nomogram was constructed using the first database. Its performance was assessed by receiver characteristic (ROC) analysis. The nomogram was externally validated in the two independent cohorts. RESULTS: A preoperative nomogram based on the clinical tumour size (P<0.001), clinical nodal status (P<0.001), oestrogen (P=0.17) and progesterone receptors (P=0.04) was developed. The nomogram accuracy was 87.3% (95% confidence interval (CI), 84.45-90.2%). Overall, the area under the ROC curve (AUC) was 86.1% for the validation set from the Institut Curie-René Huguenin, and 63.8% for the MD Anderson validation set. The negative predictive value (NPV) was high in the three cohorts (97-99%). CONCLUSIONS: We developed and validated a strong metastasis risk calculator that can evaluate with high accuracy an individual's risk of harbouring synchronous metastases at diagnosis of primary BC. CONDENSED ABSTRACT: A nomogram to predict synchronous metastases at diagnosis of breast cancer was developed and externally validated. This tool allows avoiding unnecessary expensive work-up.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/patologia , Nomogramas , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Bases de Dados Factuais , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Período Pré-Operatório , Curva ROC , Risco , Adulto JovemRESUMO
OBJECTIVE: Mucinous (colloid) breast carcinoma accounts for 1-6% of all breast cancer. It comprises pure mucinous tumours and mixed infiltrating ductal carcinomas with a mucinous component. As this latter mixed form has a worse prognosis than pure colloid carcinoma, making this diagnosis on fine needle aspiration cytology (FNAC) might influence the choice of treatment. METHODS: We report a consecutive series of 22 cases consisting of 17 mixed and five pure mucinous carcinomas diagnosed by cytology and verified on histopathology. Patients underwent FNAC at the one-stop clinic of our institution during a 7-year period of time. Cytological findings were evaluated by a semi-quantitative method and included percentage of smear surface occupied by mucin, shape of cell groupings, size and outline of tumour nuclei as well as presence or absence of nucleolus. RESULTS: Three of five pure mucinous carcinomas displayed at least two of the following features: abundant mucin, small nuclei and/or regular nuclear outlines. Sparse mucin, large nuclei, irregular nuclear outlines or the presence of nucleoli were found in 7 out of 17 mixed mucinous carcinomas but not in pure tumours. CONCLUSION: Cytopathological identification of patients with pure mucinous carcinomas may be performed in a limited number of cases.
Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Mama/patologia , Idoso , Idoso de 80 Anos ou mais , Axila/patologia , Biópsia por Agulha Fina/métodos , Feminino , Humanos , Linfonodos/patologia , Mastectomia Segmentar/métodos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The aim of neoadjuvant chemotherapy is to increase the likelihood of successful breast conservation surgery (BCS). Accurate identification of BCS candidates is a diagnostic challenge. Breast Cancer Index (BCI) predicts recurrence risk in estrogen receptor+lymph node-breast cancer. Performance of BCI to predict chemosensitivity based on pathological complete response (pCR) and BCS was assessed. METHODS: Real-time RT-PCR BCI assay was conducted using tumor samples from 150 breast cancer patients treated with neoadjuvant chemotherapy. Logistical regression and c-index were used to assess predictive strength and additive accuracy of BCI beyond clinicopathologic factors. RESULTS: BCI classified 42% of patients as low, 35% as intermediate and 23% as high risk. Low BCI risk group had 98.4% negative predictive value (NPV) for pCR and 86% NPV for BCS. High versus low BCI group had a 34 and 5.8 greater likelihood of achieving pCR and BCS, respectively (P=0.0055; P=0.0022). BCI increased c-index for pCR (0.875-0.924; P=0.017) and BCS prediction (0.788-0.843; P=0.027) beyond clinicopathologic factors. CONCLUSIONS: BCI significantly predicted pCR and BCS beyond clinicopathologic factors. High NPVs indicate that BCI could be a useful tool to identify breast cancer patients who are not eligible for neoadjuvant chemotherapy. These results suggest that BCI could be used to assess both chemosensitivity and eligibility for BCS.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos RetrospectivosRESUMO
INTRODUCTION: Organized and individual breast screening have been accompanied by an increase in the detection of "atypical breast lesions (ABL)". Recently, the NOMAT multicenter study proposed a predictive model of the risk of developing breast cancer after detection of an ABL in order to avoid surgical removal of "low-risk" lesions. It also aimed to provide information on psychological experience, in particularly anxiety, to assist in the shared medical decision process. METHODS: Three hundred women undergoing surgery for ABL were included between 2015 and 2018 at 18 French centers. Women completed questionnaires before and after surgery assessing their level of anxiety (STAI-State, STAI-Trait), their level of tolerance to uncertainty, their perceived risk of developing a breast cancer, and their satisfaction with the management care. RESULTS: One hundred nighty nine patients completed the STAI-Status before and after surgery. Overall, a decrease in anxiety level (35.4 vs 42.7, P<0.001) was observed. Anxious temperament and greater intolerance to uncertainty were significantly associated swith decreased anxiety (33%), whereas younger age was associated with increased anxiety (8%). CONCLUSION: Surgery for ABL seems to be associated with only a few cases with an increase in anxiety and seems to increase the perception of the risk of developing breast cancer. Taking into account the psychological dimension remains in all cases essential in the process of shared therapeutic decision.
Assuntos
Ansiedade , Neoplasias da Mama , Ansiedade/diagnóstico , Ansiedade/psicologia , Mama , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
PURPOSE: Although a potential role of the Epstein-Barr virus (EBV) in the pathogenesis of breast cancer (BC) has been underlined, results remain conflicting. Particularly, the impact of EBV infection on biological markers of BC has received little investigation. METHODS: In this study, we established the frequency of EBV-infected BC using real-time quantitative PCR (RT-PCR) in 196 BC specimens. Biological and pathological characteristics according to EBV status were evaluated. RESULTS: EBV DNA was present in 65 of the 196 (33.2%) cases studied. EBV-positive BCs tended to be tumours with a more aggressive phenotype, more frequently oestrogen receptor negative (P=0.05) and with high histological grade (P=0.01). Overexpression of thymidine kinase activity was higher in EBV-infected BC (P=0.007). The presence of EBV was weakly associated with HER2 gene amplification (P=0.08). CONCLUSION: Our study provides evidence for EBV-associated BC undergoing distinct carcinogenic processes, with more aggressive features.
Assuntos
Biomarcadores Tumorais/isolamento & purificação , Neoplasias da Mama/patologia , Herpesvirus Humano 4/isolamento & purificação , Sequência de Bases , Biomarcadores Tumorais/genética , Neoplasias da Mama/virologia , Primers do DNA , DNA Viral/análise , Feminino , Genes erbB-2 , Genoma Viral , Herpesvirus Humano 4/genética , Humanos , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Prognostic impact of lymph node micro-metastases (pN1mi) has been discordantly reported in the literature. The need to clarify this point for decision-making regarding adjuvant therapy, particularly for patients with endocrine receptor (ER)-positive status and HER2-negative tumors, is further reinforced by the generalization of gene expression signatures using pN status in their recommendation algorithm. PATIENTS AND METHODS: We retrospectively analyzed 13 773 patients treated for ER-positive breast cancer in 13 French cancer centers from 1999 to 2014. Five categories of axillary lymph node (LN) status were defined: negative LN (pN0i-), isolated tumor cells [pN0(i+)], pN1mi, and pN1 divided into single (pN1 = 1) and multiple (pN1 > 1) macro-metastases (>2 mm). The effect of LN micro-metastases on outcomes was investigated both in the entire cohort of patients and in clinically relevant subgroups according to tumor subtypes. Propensity-score-based matching was used to balance differences in known prognostic variables associated with pN status. RESULTS: As determined by sentinel LN biopsy, 9427 patients were pN0 (68.4%), 546 pN0(i+) (4.0%), 1446 pN1mi (10.5%) and 2354 pN1 with macro-metastases (17.1%). With a median follow-up of 61.25 months, pN1 status, but not pN1mi, significantly impacted overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and breast-cancer-specific survival. In the subgroup of patients with known tumor subtype, pN1 = 1, as pN1 > 1, but not pN1mi, had a significant prognostic impact on OS. DFS and MFS were only impacted by pN1 > 1. Similar results were observed in the subgroup of patients with luminal A-like tumors (n = 7101). In the matched population analysis, pN1macro, but not pN1mi, had a statistically significant negative impact on MFS and OS. CONCLUSION: LN micro-metastases have no detectable prognostic impact and should not be considered as a determining factor in indicating adjuvant chemotherapy. The evaluation of the risk of recurrence using second-generation signatures should be calculated considering micro-metastases as pN0.
Assuntos
Neoplasias da Mama , Neoplasias da Mama/genética , Feminino , Humanos , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Biópsia de Linfonodo SentinelaRESUMO
BACKGROUND: We determined the prognostic impact of lymphovascular invasion (LVI) in a large, national, multicenter, retrospective cohort of patients with early breast cancer (BC) according to numerous factors. PATIENTS AND METHODS: We collected data on 17 322 early BC patients treated in 13 French cancer centers from 1991 to 2013. Survival functions were calculated using the Kaplan-Meier method and multivariate survival analyses were carried out using the Cox proportional hazards regression model adjusted for significant variables associated with LVI or not. Two propensity score-based matching approaches were used to balance differences in known prognostic variables associated with LVI status and to assess the impact of adjuvant chemotherapy (AC) in LVI-positive luminal A-like patients. RESULTS: LVI was present in 24.3% (4205) of patients. LVI was significantly and independently associated with all clinical and pathological characteristics analyzed in the entire population and according to endocrine receptor (ER) status except for the time period in binary logistic regression. According to multivariate analyses including ER status, AC, grade, and tumor subtypes, the presence of LVI was significantly associated with a negative prognostic impact on overall (OS), disease-free (DFS), and metastasis-free survival (MFS) in all patients [hazard ratio (HR) = 1.345, HR = 1.312, and HR = 1.415, respectively; P < 0.0001], which was also observed in the propensity score-based analysis in addition to the association of AC with a significant increase in both OS and DFS in LVI-positive luminal A-like patients. LVI did not have a significant impact in either patients with ER-positive grade 3 tumors or those with AC-treated luminal A-like tumors. CONCLUSION: The presence of LVI has an independent negative prognostic impact on OS, DFS, and MFS in early BC patients, except in ER-positive grade 3 tumors and in those with luminal A-like tumors treated with AC. Therefore, LVI may indicate the existence of a subset of luminal A-like patients who may still benefit from adjuvant therapy.
Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Prognóstico , Estudos RetrospectivosRESUMO
The purpose of this investigation was to determine the diagnostic accuracy of quantitative real-time polymerase chain reaction (PCR) assay in diagnosing bacterial vaginosis versus the standard methods, the Amsel criteria and the Nugent score. The Amsel criteria, the Nugent score, and results from the molecular tool were obtained independently from vaginal samples of 163 pregnant women who reported abnormal vaginal symptoms before 20 weeks gestation. To determine the performance of the molecular tool, we calculated the kappa value, sensitivity, specificity, and positive and negative predictive values. Either or both of the Amsel criteria (≥3 criteria) and the Nugent score (score ≥7) indicated that 25 women (15%) had bacterial vaginosis, and the remaining 138 women did not. DNA levels of Gardnerella vaginalis or Atopobium vaginae exceeded 10(9) copies/mL or 10(8) copies/mL, respectively, in 34 (21%) of the 163 samples. Complete agreement between both reference methods and high concentrations of G. vaginalis and A. vaginae was found in 94.5% of women (154/163 samples, kappa value = 0.81, 95% confidence interval 0.70-0.81). The nine samples with discordant results were categorized as intermediate flora by the Nugent score. The molecular tool predicted bacterial vaginosis with a sensitivity of 100%, a specificity of 93%, a positive predictive value of 73%, and a negative predictive value of 100%. The quantitative real-time PCR assay shows excellent agreement with the results of both reference methods for the diagnosis of bacterial vaginosis.
Assuntos
Violeta Genciana , Fenazinas , Reação em Cadeia da Polimerase/métodos , Complicações Infecciosas na Gravidez/diagnóstico , Vaginose Bacteriana/diagnóstico , Actinobacteria/genética , Actinobacteria/isolamento & purificação , Adulto , Feminino , Gardnerella vaginalis/genética , Gardnerella vaginalis/isolamento & purificação , Humanos , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Sensibilidade e Especificidade , Coloração e Rotulagem , Vagina/microbiologia , Vaginose Bacteriana/microbiologia , Adulto JovemRESUMO
Achieving a mastectomy occurs in one third of the acts of breast cancer surgery. In the present context, the increase in the diagnosis of early breast cancer, including widespread or multifocal forms, the possibility of a reconstruction at the same time is discussed. It will be proposed in a specific context, taking into account various factors: oncological (characteristics of the tumor, adjuvant treatments), clinical (smoking, comorbidity) and psychological (choice of the patient). The technique of mastectomy will be adapted to the indication and choice of reconstruction procedure. Including the preservation of the nipple-areola complex, or the skin envelope will be possible for some guidance. The reconstruction is possible with the use of breast implants, or musculocutaneous flaps or by the combination of both. Some of these techniques are associated with significant morbidity, and appropriate selection of procedure to the patient will guarantee a lower risk of complications.
Assuntos
Implantes de Mama , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia/métodos , Mamilos/cirurgia , Neoplasias da Mama/psicologia , Feminino , Humanos , Satisfação do Paciente , Retalhos Cirúrgicos , Fatores de Tempo , Resultado do TratamentoRESUMO
Collagen IV is a major component of the vascular basement membrane and may be a marker of angiogenesis. Serum levels of this protein are elevated in some human cancers. Our objectives were to compare collagen IV levels in the serum of breast cancer patients and healthy women and to examine changes during preoperative chemotherapy. Sera from 51 patients with stage II-III breast cancer and 55 healthy controls were analysed. Collagen IV level was measured by a commercially available sandwich enzyme link immunoassay. Baseline serum levels were compared between cancer patients and healthy women and paired pre- and post-chemotherapy measurements were also performed in 39 patients who received preoperative chemotherapy and were correlated with response to therapy. The median serum collagen IV concentration was significantly higher in cancer patients (166 microg l(-1)) than in healthy women (115 microg l(-1)), P<0.001. Chemotherapy induced a significant further increase in serum collagen IV (167 microg l(-1) prechemo vs 206 microg l(-1) postchemo, P=0.001). There were no correlations between baseline collagen IV levels and response to therapy, age, clinical stage or HER2 status. In conclusion, patients with breast cancer have elevated levels of collagen IV compared to healthy women and collagen IV levels increase further during chemotherapy.
Assuntos
Neoplasias da Mama/sangue , Colágeno Tipo IV/sangue , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Terapia NeoadjuvanteRESUMO
BACKGROUND: Phosphorylation of serine 118 (ser118) has been reported to be involved in the activation of estrogen receptor (ER). In the present study, we evaluated whether endocrine therapy modulated ER phosphorylation on ser118. PATIENTS AND METHODS: We carried out a tissue microarray that included 80 primary breast tumors obtained before the administration of endocrine therapy. A second tissue microarray included 52 tumors obtained after endocrine therapy from the same patients. Immunostainings were carried out for ER, Pser118ER, Her2, insulin growth factor receptor (IGFR), p21-activated kinase 1 (PAK1), pMAPK, bcl2 and progesterone receptor. RESULTS: Pser118ER staining was higher in Her2- (P = 0.06), IGFR- (P = 0.0002) and pMAPK-expressing tumors (P = 0.001). The level of ER phosphorylation was not different according to the occurrence of clinical tumor response (P = 0.16). Pser118ER expression was significantly reduced by endocrine therapy. The mean Pser118ER score was 163 [standard deviation (SD) 81] before endocrine therapy and 80 (SD 90) after endocrine therapy (P = 0.0001, paired t-test). The magnitude of Pser118ER decrease was higher in tumors that responded to endocrine therapy (mean decrease 128, SD 86) as compared with refractory tumors (mean decrease 38, SD 130) (P = 0.017, t-test). CONCLUSION: These findings suggest that endocrine therapy modulates ER on ser118. Pser118ER immunostaining could be used as surrogate marker to monitor treatment efficacy.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptores de Estrogênio/metabolismo , Adenocarcinoma/patologia , Idoso , Inibidores da Aromatase/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Receptor IGF Tipo 1/metabolismo , Serina/metabolismo , Tamoxifeno/uso terapêuticoRESUMO
OBJECTIVE: To compare maternal morbidity after Thierry's spatulas or vacuum-assisted deliveries. PATIENTS AND METHODS: Retrospective study, at the French hospital la Conception, in Marseilles. All successful instrumental deliveries between November 2003 and May 2005 were reviewed, that is to say 264. Univariate and multivariate analysis were performed comparing maternal morbidity in the two groups. The primary outcome measure was perineal trauma. Secondary outcomes were blood loss and duration of hospitalization. RESULTS: Among the 264 deliveries, there were 96 vacuum deliveries and 168 Thierry's spatulas extraction. Thierry's spatulas were use more often in nulliparous patient (<0.001). Patients in the group of Thierry's spatulas have a higher rate of epidural analgesia (p=0.05), a longer duration of first (p=0.002) and second stage of labor (p=0.03). There was no difference in incidence of sphincter tears between women who underwent Thierry's spatulas and those who underwent vacuum delivery with respective incidence of 4.2 and 3.2% (p=0.67). There was a significant difference in post-partum hemoglobin value with a higher blood loss in the group of Thierry's spatulas (<0.001). Mean duration of hospitalization was longer in the group with Thierry's spatulas (5.6 days) than in the group who underwent vacuum delivery (4.7 days) (p<0.001). DISCUSSION AND CONCLUSION: Incidence of third degree tears was similar between the vacuum and Thierry's spatulas group. Deliveries with vacuum are associated with less blood loss and a shorter hospitalization stay.
Assuntos
Parto Obstétrico/métodos , Extração Obstétrica/instrumentação , Lacerações/etiologia , Períneo/lesões , Hemorragia Pós-Parto/etiologia , Vácuo-Extração/efeitos adversos , Adulto , Parto Obstétrico/efeitos adversos , Feminino , Humanos , Lacerações/epidemiologia , Tempo de Internação , Forceps Obstétrico/efeitos adversos , Paridade , Hemorragia Pós-Parto/epidemiologia , Gravidez , Estudos Retrospectivos , Fatores de Risco , Vácuo-Extração/métodosRESUMO
BACKGROUND: Prion protein (PrPc) has been previously reported to be associated with resistance to proapoptotic stimuli. We evaluated whether the expression of PrPc was associated with the resistance to adjuvant chemotherapy in patients with estrogen receptor (ER) -negative breast cancer. PATIENTS AND METHODS: The expression of PrPc by primary tumors was assessed by immunohistochemistry in a series of 756 patients included in two randomized trials that compared anthracycline-based chemotherapy to no chemotherapy. The PrPc expression was correlated with ER expression and the benefit of adjuvant chemotherapy was assessed according to PrPc expression in patients with ER-negative tumors. RESULTS: Immunostaining analysis showed that PrPc was mainly expressed by myoepithelial cells in normal breast tissue. Tissue microarray analysis from 756 breast tumors showed that PrPc was associated with ER-negative breast cancer subsets (P < 0.001). Adjuvant chemotherapy was not associated with a significant risk reduction for death in patients with ER-negative/PrPc-positive disease [adjusted hazard ratio (HR) for death = 0.98, 95% confidence interval (CI) 0.45-2.1, P = 0.95], while it decreased the risk for death (HR = 0.39, 95% CI 0.2-0.74, P = 0.004) in patients with ER-negative/PrPc-negative tumors. CONCLUSION: These data indicate that ER-negative/PrPc-negative phenotype is associated with a high sensitivity to adjuvant chemotherapy.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Proteínas PrPC/metabolismo , Receptores de Estrogênio/análise , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Mastectomia/métodos , Pessoa de Meia-Idade , Proteínas PrPC/genética , Probabilidade , Prognóstico , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do TratamentoRESUMO
Placenta accreta is a life-threatening obstetrical condition requiring a multidisciplinary approach. Despite identified obstetrical risk factors, the diagnosis is often made at the time of delivery. Recent advances in biology could allow a prenatal screening of placenta accreta with the identification of biological markers in maternal blood including cell-free fetal DNA, placental mRNA, and DNA microarray. These promising technologies can detect the presence of anomalies and should play a future role in developing a better understanding of placental invasion. Ultrasound imaging is popular due to its low cost and accessibility and widely used for the screening of placenta location and potential abnormal development. This exam is associated with high sensitivity and specificity for diagnosis of placenta accreta when specific defined criteria are used for the diagnosis. A placental MRI provides a morphological description, as well as recently demonstrated topographical information that optimizes diagnosis and surgical management. The screening of placenta accreta should be improved with the use of a combination of these diagnostic techniques and benefit high-risk populations with a reduction in morbidity.
Assuntos
Placenta Acreta/diagnóstico , Diagnóstico Pré-Natal/métodos , Biomarcadores/análise , Feminino , Humanos , Placenta Acreta/diagnóstico por imagem , Gravidez , UltrassonografiaRESUMO
OBJECTIVE: This study was undertaken to evaluate prevalence of low urinary tract symptoms (LUTS) after Thierry's spatula delivery at first pregnancy. PATIENTS AND METHODS: A retrospective study of 236 primiparous with instrumental delivery or spontaneous delivery who had delivered from January 2001 to December 2002. Low urinary tract symptoms (LUTS) were evaluated one year after delivery with a questionnaire. Incidence of LUTS was compared depending on mode of delivery. RESULTS: Of the 236 patients included, 88.1% replied to the questionnaire, 106 who delivered spontaneously and 102 who underwent Thierry's spatula delivery. The incidence of urinary incontinence was similar after instrumental deliveries and after spontaneous vaginal deliveries (34.9 versus 24.5%, p=0.10). In univariate analysis, symptoms of urinary urgency and urinary frequency were higher after instrumental delivery than after spontaneous delivery, respectively, 34.9 versus 22.5%, p=0.049 and 19.8 versus 8.8%, p=0.03. After controlling for confounding factors, no difference in LUTS was observed between the two groups; the respective adjusted odds-ratios (95% IC) were 1,5 (0.8-3) for urinary incontinence, 1.7 (0.9-3.5) for urgency and 2.5 (0.9-6.3) for urinary frequency. DISCUSSION AND CONCLUSION: One year after delivery, one third of patients will present urinary incontinence and more than 50% will complain of bladder instability symptoms. Compared to spontaneous vaginal delivery, the use of Thierry's spatulas at first pregnancy does not induce higher risk of LUTS.